Parasympathetic, but not sympathetic denervation, suppressed colorectal cancer progression.

Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However, the underlying mechanisms are not still fully understood. Therefore, the present study aimed to evaluate the effects of sympathetic and parasympathetic denervation on the inhibition of colorectal cancer progression in early and late phases and assess the involvement of nerve growth factor in denervation mediated anticancer effects. One-hundred and fifty male Wistar rats were assigned into 15 groups. Seven groups comprising the control group, 1,2-dimethylhydrazine (DMH) group, sympathetic denervation group (celiac-mesenteric ganglionectomy and guanethidine sulphate administration), parasympathetic denervation group (vagotomy and atropine administration), and combination group were used in the early-stage protocol. For the late-stage protocol, eight groups comprising the control, DMH, surgical and pharmacological sympathetic and parasympathetic denervation groups, combination group, and 5-flourouracil group were considered. After 8 weeks, sympathetic and parasympathetic denervation significantly reduced ACF numbers in rats receiving DMH. On the other hand, in the late stages, parasympathetic but not sympathetic denervation resulted in significant reductions in tumor incidence, tumor volume and weight, cell proliferation (indicated by reduced immunostaining of PCNA and ki-67), and angiogenesis (indicated by reduced immunostaining of CD31 and VEGF expression levels), and downregulated NGF, ß2 adrenergic, and M3 receptors. It can be concluded that parasympathetic denervation may be of high importance in colon carcinogenesis and suggested as a possible therapeutic modality in late stages of colorectal cancer.

5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract.

BACKGROUND: In the gastrointestinal tract of several species, facilitating 5-HT4 receptors were proposed on myenteric cholinergic neurons innervating smooth muscle by in vitro study of the effect of the selective 5-HT4 receptor agonist prucalopride on submaximal cholinergic contractions. This was not yet established in the murine gastrointestinal tract. METHODS: In circular smooth muscle strips from murine fundus, jejunum and colon, contractions were induced by electrical field stimulation in the presence of guanethidine, L-NAME and for colon also MRS 2500. Submaximal contractions were induced to study the influence of prucalopride. KEY RESULTS: Electrical field stimulation at reduced voltage induced reproducible submaximal neurogenic and cholinergic contractions as the contractions were abolished by tetrodotoxin and atropine. Hexamethonium had no systematic inhibitory effect but mecamylamine reduced the responses, suggesting that part of the cholinergic response is due to activation of preganglionic neurons. Prucalopride concentration-dependently increased the submaximal cholinergic contractions in the three tissue types, reaching maximum from 0.03 µmol/L onwards. The facilitation in the different series with 0.03 µmol/L prucalopride ranged from 41% to 104%, 30% to 76% and 24% to 74% in fundus, jejunum, and colon, respectively. The effect of 0.03 µmol/L prucalopride was concentration-dependently inhibited by GR 113808. CONCLUSIONS & INFERENCES: In the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species.

Renal denervation by CT-guided periarterial injection of hyperosmolar saline, vincristine, paclitaxel and guanethidine in a pig model.

AIMS: The aim of the study was to evaluate the feasibility, safety and efficacy of renal sympathetic denervation with CT-guided periarterial injection of potentially neurolytic agents in pigs. METHODS AND RESULTS: Unilateral injection of formulations containing either 5M hyperosmolar saline, vincristine, paclitaxel or guanethidine around the renal artery was performed in 24 normotensive pigs with six animals per group. Needle placement and injections were performed under CT fluoroscopy guidance. Blood pressure measurements and CT scans were performed immediately before and after the intervention and four weeks after treatment. After euthanasia, norepinephrine (NE) concentrations of both kidneys were determined. The renal arteries and surrounding tissue were examined histologically to evaluate nerve fibre degeneration. Procedures were technically successful with good periarterial distribution of the injectant in all but one pig in the guanethidine group. No major adverse events or post-interventional complications occurred. In the vincristine group, NE concentrations of the renal parenchyma were lower on the treated side in all pigs with a mean decrease of 53% (38%-62%, p<0.01) compared to the contralateral control. Correspondingly, histological examination revealed neural degeneration in all animals treated with vincristine. In the other groups, no significant drop of NE values, or histological signs of nerve fibre degeneration were found. CONCLUSIONS: CT-guided periarterial injection of the different substances was feasible and safe. Renal sympathetic denervation was achieved with vincristine. In contrast, hyperosmolar saline, paclitaxel and guanethidine do not seem to be appropriate for renal denervation in a pig model at the dosage used.

Sympathetic fiber sprouting in inflamed joints and adjacent skin contributes to pain-related behavior in arthritis.

Although chronic pain is the most common symptom of arthritis, relatively little is known about the mechanisms driving it. Recently, a sprouting of autonomic sympathetic fibers into the upper dermis of the skin, an area that is normally devoid of them, was found in the skin following chronic inflammation of the rat hindpaw. While this sprouting only occurred when signs of joint and bone damage were present, it remained to be clarified whether it was a consequence of the chronic inflammation of the skin or of the arthritis and whether it also occurred in the joint. In the present study, we used a model of arthritis in which complete Freund's adjuvant (CFA) was injected into the rat ankle joint. At 4 weeks following CFA treatment, there was an increase in sympathetic and peptidergic fiber density in the ankle joint synovium. We also observed a sympathetic, but not peptidergic, fiber sprouting in the skin over the joint, which may be a consequence of the increased levels of mature nerve growth factor levels in skin, as revealed by Western blot analysis. The pharmacological suppression of sympathetic fiber function with systemic guanethidine significantly decreased the pain-related behavior associated with arthritis. Guanethidine completely suppressed the heat hyperalgesia and attenuated mechanical and cold hypersensitivity. These results suggest that transmitters released from the sprouted sympathetic fibers in the synovial membrane and upper dermis contribute to the pain-related behavior associated with arthritis. Blocking the sympathetic fiber sprouting may provide a novel therapeutic approach to alleviate pain in arthritis.

Combined effect of sildenafil and guanethidine, propranolol or verapamil on erectile function in rats.

OBJECTIVES: This study aims to further elucidate the role of adrenergic transmission in erection and to highlight whether adrenergic transmission in the penis modulates sildenafil's action. METHODS: Measurement of intracavernosal pressure in the anesthetized rat model. KEY FINDINGS: Guanethidine (3 and 6 mg/kg) potentiated intracavernosal pressure/mean arterial pressure (ICP/MAP) rises in response to cavernous nerve stimulation by 4.375 ± 0.425 and 18.375 ± 1.085% respectively. Propranolol did the opposite. In presence of guanethidine, sildenafil (0.01, 0.1 and 1 mg/kg) potentiated ICP/MAP responses by 81.571 ± 4.918%, 147.83 ± 10.864% and 279.285 ± 23.053% at 1 Hz compared to 22.277 ± 2.139%, 123.571 ± 8.443% and 186.25 ± 13.542% respectively in the absence of guanethidine. Propranolol inhibited the effect sildenafil at all frequencies of stimulation. Verapamil exhibited a pro-erectile action and potentiated the effect of sildenafil (0.01, 0.1 and 1 mg/kg) on erectile responses corresponding to 85.25 ± 6.716%, 146 ± 11.288% and 221.571 ± 19.032% respectively compared to 26.011 ± 1.911%, 87.142 ± 8.73% and 182.2 ± 16.921% in its absence. CONCLUSIONS: This study provides functional evidence that inhibition of sympathetic tone peripherally results in enhancement of erectile function. ß-adrenergic receptors seem to play an important role in erection. The combination of sildenafil and guanethidine or verapamil could have a potential advantage on erectile function but propranolol may mask the effect of sildenafil on erectile function.

Gender- and age-related differences in muscular and nerve-mediated responses in human colon.

BACKGROUND: Gender- and age-related differences in muscular and nerve-mediated responses in human colon are poorly characterized. We studied carbachol-induced motor responses and electrically evoked contractions in sigmoid circular muscle from adult and elderly patients of different gender. METHODS: Sigmoid colon segments were obtained from 24 men and 16 women undergoing left hemicolectomy for colon cancer. Isometric tension was measured on muscle strips exposed to increasing carbachol concentrations. The effects of atropine, guanethidine, L-nitro arginine methyl ester (L-NAME), and tetrodotoxin on electrically evoked contractions were also studied. RESULTS: Female patients showed higher maximal response to carbachol than male patients, elderly females being the most sensitive to carbachol among all patient groups. Electrically evoked contractions were linearly related to stimulation frequency and abolished by tetrodotoxin. Electrically evoked contractions were significantly more pronounced in elderly male patients; they were reduced by atropine and guanethidine and increased by L-nitro arginine methyl ester in the presence of atropine and guanethidine (P < 0.05). The effect of L-NAME was most marked in elderly male patients and least pronounced in elderly females. CONCLUSIONS: The response to carbachol and the role of nitrergic pathways differ according to age and gender; this may depend on muscarinic receptor upregulation or humoral factors affecting nitric oxide release, respectively.

Nitric oxide and carbon monoxide act as inhibitory neurotransmitters in the longitudinal muscle of C57BL/6J mouse distal colon.

The present study was designed to identify the inhibitory neurotransmitters mediating nonadrenergic noncholinergic relaxation in the longitudinal muscle of C57/BL mouse distal colon. Relaxation induced by electrical field stimulation (EFS) was recorded isotonically in the presence of atropine and guanethidine. Cyclic guanosine-3',5'-monophosphate (cyclic GMP) content was measured by radioimmunoassay. EFS-induced relaxation was inhibited by nitro-L-arginine (L-NNA) and Sn (IV) protoporphyrin dichloride IX (SnPP-IX), a nitric oxide (NO) and carbon monoxide (CO) synthase inhibitor, respectively. A combination of both inhibitors produced an additive effect. ODQ, a soluble guanylate cyclase inhibitor, inhibited EFS-induced relaxation. NOR-1, a NO donor, and carbon monoxide-releasing molecule-2 (CORM-2), a CO donor, treatment relaxed the distal colon and increased cyclic GMP content. The effects of NOR-1 and CORM-2 were inhibited by ODQ. KT5823, a cyclic GMP-dependent protein kinase inhibitor, inhibited EFS-induced relaxation. EFS-induced relaxation in the presence of KT5823 was further inhibited by L-NNA, but not by SnPP-IX. In addition, KT5823 inhibited CORM-2-induced relaxation, but not NOR-1-induced relaxation. H89, a cyclic AMP-dependent protein kinase inhibitor, inhibited EFS-induced relaxation, and EFS-induced relaxation in the presence of H89 was further inhibited by L-NNA. These results suggested that NO and CO function as inhibitory neurotransmitters in the longitudinal muscle of C57BL mouse distal colon.

Functional characterization of nonadrenergic noncholinergic neurotransmitter release via endocannabinoids: an in vitro study in rabbit corpus cavernosum.

INTRODUCTION: Corporal smooth muscle relaxation is mediated mainly but not completely by nitric oxide. Endocannabinoids modulate the various neurotransmitter systems. AIM: In the present study, a possible role of endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated relaxations was investigated. METHODS: In precontracted tissues, control electrical field stimulation (EFS)-induced NANC relaxation responses were obtained using varying frequencies of stimulation in the presence of L-arginine methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar experimental procedure was applied in the presence of cannabinoid receptor antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA), or JHW015. MAIN OUTCOME MEASURES: Effects of cannabinoid receptor antagonists and agonists on EFS-evoked non-nitrergic NANC relaxation responses. RESULTS: L-NAME abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and AM630 either together or separately inhibited, whereas anandamide, ACEA, and JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630. Capsazepine enhanced non-nitrergic NANC relaxation responses. CONCLUSION: These results suggest that non-nitrergic NANC relaxations may be mediated partially by cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and cannabinoid CB(2) receptors.

Guanethidine treatment does not block the ability of central leptin administration to decrease blood glucose concentrations in streptozotocin-induced diabetic rats.

Leptin, administered either into the ventricles of the brain or systemically, has been shown to normalize blood glucose concentrations in streptozotocin (STZ)-induced diabetic rats. We hypothesized that an intact sympathetic nervous system is necessary for centrally administered leptin to normalize or attenuate high blood glucose concentrations in STZ-induced diabetic rats. Young male Wistar rats (approximately 50 g) were treated every other day with either s.c. guanethidine (100 mg/kg) or vehicle for 2 weeks. Rats were then implanted with an intracerebroventricular cannula directed to the lateral ventricle and made diabetic with an i.v. injection of STZ (50 mg/kg). Half of the animals in each group were given daily injections of leptin (10 microl), while the remaining animals received vehicle injections. Blood glucose concentrations were measured daily and tissue norepinephrine content was determined by high performance liquid chromatography at the end of the study. Guanethidine pretreatment did not block the ability of centrally administered leptin to decrease blood glucose concentrations in diabetic rats. This suggests that the sympathetic nervous system does not mediate the leptin-induced attenuation of high blood glucose concentrations observed in diabetic rats.

Sympathectomy alters bone architecture in adult growing rats.

Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone.

[Use of ilio-inguinal iliohypogastric nerve block for herniorraphy: a prospective study in a 35-case series at the Lome University Hospital Center in Togo]. / Pratique du bloc ilio-inguinal ilio-hypogastrique pour cure herniaire: étude prospective à propos de 35 cas colligés au CHU de Lomé, Togo.

The purpose of this prospective-descriptive study was to evaluate the quality of anaesthesia and analgesic effect achieved by ilio-inguinal iliohypogastric nerve block (IINB) in patients undergoing herniorraphy. Study was carried out over a 6-month period in the Anaesthesia Intensive Care Department of the Lomé University Hospital Centre in Togo. All patients indicated for unilateral herniorraphy were enrolled. A total of 35 patients underwent herniorraphy with IINB. Mean patient age was 32 years. Farmers accounted for 57% of the population. Men accounted for 86.7%. The anaesthesia classification was ASA I or II in 88.6% of cases. Complete sensory block was obtained within 15 minutes after induction in 71.43% of cases. Additional sedation using ketamine and/or fentanyl was used in 51.43% of cases. Conversion from IINB to general anaesthesia was necessary in three cases including 2 due to extension of the surgical incision and one for the surgeon's convenience. The mean duration of the procedure was 70 minutes. Intraoperative complications included nausea in one case, dizziness in 2 cases, and bitterness in mouth in 3 cases. Postoperatively, extension to the femoral nerve was observed in 2 cases. Five patients presented a visual analogue pain scale (VAS) > or = 4 within 18 hours after the procedure. This study shows that IINB is a useful alternative to general anaesthesia for herniorraphy. Specific training is necessary to allow more widespread use.

Depletion of noradrenaline inhibits electrically-evoked pain in the skin of the human forearm.

Guanethidine displaces noradrenaline from sympathetic varicosities, and blocks sympathetic noradrenergic neurotransmission by inhibiting the release of noradrenaline from depleted neural stores. The aim of this study was to determine whether depletion of noradrenaline with guanethidine would oppose thermal hyperalgesia and/or electrically-evoked pain in mildly-burnt skin. Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. The heat-pain threshold to a temperature gradient that increased at 0.5 degrees C/s was then measured at the guanethidine site, a nearby saline-control iontophoresis site, and in untreated skin. In addition, participants rated pain intensity to a 47 degrees C stimulus that was applied to each site for 7s. Shortly after the iontophoreses, sensitivity to heat was greater at the guanethidine site than the two control sites, suggesting that ejection of noradrenaline from sympathetic varicosities increased sensitivity to heat. One day later, when neural stores of noradrenaline were depleted, sensitivity to heat did not differ between the guanethidine and control sites. The guanethidine pretreatment did not influence thermal hyperalgesia induced by a mild burn, but inhibited pain evoked by electrical stimulation of the skin (0.2 mA direct current for 4 min). These findings indicate that ongoing sympathetic neural discharge does not normally influence thermal hyperalgesia in inflamed skin, because depleting noradrenergic stores had no effect. However, electrically-evoked release of noradrenaline may increase nociceptive sensations. Further clarification of this human pain model could provide insights into the mechanism of adrenergic hyperalgesia in certain neuropathic pain syndromes.

Delayed sympathetic dependence in the spared nerve injury (SNI) model of neuropathic pain.

BACKGROUND: Clinical and experimental studies of neuropathic pain support the hypothesis that a functional coupling between postganglionic sympathetic efferent and sensory afferent fibers contributes to the pain. We investigated whether neuropathic pain-related behavior in the spared nerve injury (SNI) rat model is dependent on the sympathetic nervous system. RESULTS: Permanent chemical sympathectomy was achieved by daily injection of guanethidine (50 mg/kg s.c.) from age P8 to P21. SNI was performed at adulthood followed by 11 weeks of mechanical and thermal hypersensitivity testing. A significant but limited effect of the sympathectomy on SNI-induced pain sensitivity was observed. The effect was delayed and restricted to cold allodynia-like behavior: SNI-related cold scores were lower in the sympathectomized group compared to the control group at 8 and 11 weeks after the nerve injury but not before. Mechanical hypersensitivity tests (pinprick and von Frey hair threshold tests) showed no difference between groups during the study period. Concomitantly, pericellular tyrosine-hydroxylase immunoreactive basket structures were observed around dorsal root ganglia (DRG) neurons 8 weeks after SNI, but were absent at earlier time points after SNI and in sham operated controls. CONCLUSION: These results suggest that the early establishment of neuropathic pain-related behavior after distal nerve injury such as in the SNI model is mechanistically independent of the sympathetic system, whereas the system contributes to the maintenance, albeit after a delay of many weeks, of response to cold-related stimuli.

Effect of darkness on upper eyelid position.

PURPOSE: To determine the magnitude of upper eyelid retraction induced by sudden darkness in normal subjects and in patients with Graves upper eyelid retraction before and after treatment with guanethidine drops. METHODS: The study comprised 211 control subjects (n=211 eyes) and 45 patients (n=78 eyes) with Graves upper eyelid retraction. The control subjects were divided in four age groups: 0 to 1 year, 2 to 9 years, 0 to 18 years, and 19 to 61 years. Twenty-one patients with Graves upper eyelid retraction (n=39 eyes) used guanethidine drops for 15 days. Palpebral fissure images of subjects were acquired in photopic conditions and in darkness. For both images, the distance between the mid-pupil and upper eyelid margin was measured. RESULTS: Darkness induced upper eyelid retraction in all subjects. The increment in the mid-pupil eyelid distance was greater in children. There was no significant difference between the magnitude of eyelid elevation of Graves patients and normal adults. Guanethidine drops did not abolish the eyelid reflex in Graves patients. CONCLUSIONS: Darkness provokes upper eyelid retraction in control subjects and in patients with Graves upper eyelid retraction. This effect decreases with age and does not result from sympathetic stimulation of the Muller muscle.

Long-term treatment with low-dose, but not high-dose, guanethidine improves ventricular function and survival of rats with heart failure after myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of various doses of guanethidine, a sympathoinhibitory drug, on ventricular function and survival in chronic heart failure (CHF) after myocardial infarction (MI) in rats. BACKGROUND: Direct inhibition of sympathetic outflow by a sympathoinhibitory drug might be an effective approach to therapy of CHF. However, recent clinical trials suggest that excessive suppression of sympathetic activity has an adverse effect on outcome. It remains unclear whether the beneficial effects of the sympathoinhibitory drug would be modified by its dosage. METHODS: Three doses of guanethidine (low-dose [LG], 1 mg/kg/day; medium-dose, 3 mg/kg/day; high-dose, 10 mg/kg/day) were administered via an osmotic mini-pump for 4 weeks. Hemodynamics, left ventricular (LV) diameters, plasma and myocardial norepinephrine (NE) levels, and survival were determined for four weeks after MI. RESULTS: As compared with MI rats receiving vehicle, LG suppressed LV dilation (9.2 +/- 0.9 mm vs. 11.0 +/- 0.8 mm, p < 0.05) and improved LV fractional shortening (25.0 +/- 4.5% vs. 16.4 +/- 4.7%, p < 0.05) in association with a reduction of plasma NE levels (520 +/- 250 pg/ml vs. 1,000 +/- 570 pg/ml, p < 0.05), but not with a significant reduction of noninfarcted myocardial NE levels (154 +/- 71 ng/g vs. 207 +/- 71 ng/g). Low-dose guanethidine reduced 24-h (6%) and 28-day mortality (6%), as compared with untreated MI rats (36% and 52%, respectively). High-dose guanethidine also reduced 24-h mortality (12%) but increased 28-day mortality (91%), in association with a depletion of myocardial NE. Medium-dose guanethidine had no beneficial effects on LV hemodynamics or long-term survival. CONCLUSIONS: These results indicate that the dosage of the sympathoinhibitory drug might be quite important for the treatment of CHF.

Effects of guanethidine administration on compensatory ovarian hypertrophy, compensatory ovulation and follicular development in the prepubertal female guinea pig.

We analyzed the participation of sympathetic ovarian innervation in the prepubertal female guinea pig on regulation of compensatory ovarian hypertrophy (COH) and compensatory ovulation at puberty. The COH of the left ovary was significantly higher that of the right one (left ovary: 41.5+/-5.2 vs. 27.5+/-5.6%, p<0.05, Kruskal-Wallis test). The sympathetic denervation induced by guanethidine administration beginnings at birth or on day 10 resulted in a significant increase of the COH by each ovary (p<0.05, Kruskal-Wallis test). Only one of the six untreated control guinea pigs sacrificed at the follicular phase ovulate. All the hemiovariectomized animals with the left ovary in situ ovulated, while only two out of five with the right ovary in situ did (100 vs. 40%: p<0.001, Kruskal-Wallis test), unlike the denervated animals, which did not ovulate. The number of corpora lutea present in the ovaries was similar among all groups of animals. These results demonstrate differences in the follicular diameter in untreated female guinea pigs and add further support to the concept of asymmetrical response of the ovaries to denervation.

Effects of functional peripheral sympathetic denervation induced by guanethidine on follicular development and ovulation of the adult female guinea pig.

The present study investigates the effects of functional sympathetic peripheral denervation induced by guanethidine sulphate (GTD) to adult female guinea pigs in the follicular (FPh) or luteal phases (LPh) on their oestrous cyclicity and ovulation. No differences were observed in oestrous cyclicity or the average number of corpora lutea present in the ovaries between the control and denervated animals. Guanethidine sulphate administration resulted in a significant decrease in ovarian norepinephrine content, higher for the left ovary than for the right one. Serum oestrogen and progesterone concentrations, the mean of follicles, and its diameter were different, depending on the oestral cycle in which the treatment was performed. These results suggest that in adult normal female guinea pigs, ovarian innervation participates in the regulation of follicular development in an inhibitory way.

Intravenous regional guanethidine blockade in the treatment of post-traumatic complex regional pain syndrome type 1 (algodystrophy) of the hand.

A total of 57 patients, aged between 23 and 86 years, with complex regional pain syndrome (CRPS) type 1 nine weeks after an isolated closed fracture of the distal radius, was randomised to receive either serial intravenous regional blockade (IVRB) with 15 mg of guanethidine in 30 ml of 0.5% prilocaine or serial IVRB with 30 ml of normal saline at weekly intervals until the tenderness in their fingers had resolved or they had received a maximum of four IVRBs. The analgesic efficacy was assessed at 24 hours, 48 hours and one week after each procedure by the dolorimetry ratio and verbal pain scores, and at intervals up to six months after the fracture. There was no significant difference in the number of IVRBs administered or in finger tenderness, stiffness or grip strength between the two groups. The guanethidine group experienced more pain in the affected hand (p = 0.025) and at six months had more vasomotor instability (p < 0.0001) compared with the control group. IVRB using guanethidine offers no significant analgesic advantage over a normal saline placebo block in the treatment of early CRPS type 1 of the hand after fracture of the distal radius. It does not improve the outcome of this condition and may delay the resolution of vasomotor instability when compared with the placebo.